Hydrochloric Acid → 2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-one

HRID 217892Notes

Reaction equation

HRID 217892 reaction equation
[N:1]1[CH2:2][CH:3]=[CH:4][CH:5]=[CH:6][C:7]=1[NH2:8].Cl.C1(=O)NCCCCC1.C(=O)([O-])[O-].[K+].[K+].[N:24]1[CH:29]=[CH:28][C:27]([C:30](=O)[CH2:31][C:32](OCC)=[O:33])=[N:26][CH:25]=1>C(O)C>[N:24]1[CH:29]=[CH:28][C:27]([C:30]2[N:8]=[C:7]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:1]3[C:32](=[O:33])[CH:31]=2)=[N:26][CH:25]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7768CaprolactamHCID 11430Potassium CarbonateHCID 11961458Ethyl 3-oxo-3-(pyrimidin-4-yl)propanoateHCID 188006272H-azepin-7-amine

Product 1

HCID 671776292-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-oneYield 28.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a suspension of 77.9 g (524.1 mmol) of 2H-azepin-7-amine, 3,4,5,6-tetrahydro, monohydrochloride (synthesis as described in WO96/14844 or Journal of Medicinal Chemistry (1998), 41(9), 1361-1366 or by analogy with the method described in example 1, step 1.1. and 1.2 using ε-caprolactam instead of (+/−)-3-phthalimidopiperidin-2-one) in 390 mL of ethanol was added 72.4 g (524.1 mmol) of potassium carbonate. The reaction mixture was stirred at room temperature for 10 min, 101.7 g (524.1 mmol) of ethyl 3-(4-pyrimidinyl)-3-oxopropionate was added and the resulting mixture was stirred under reflux for 16 h. The cooled solution was evaporated to remove solvent. The mixture was dissolved in dichloromethane, washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate and evaporated to dryness. The residue was filtrate through a pad of silica, rinsing with dichloromethane and then ethyl acetate. After evaporation, the resulting solid was triturated with diethyl ether to afford 36.4 g (28%) of pure product as a white-brown powder.

Workup

  1. customsynthesis
  2. stirringthe resulting mixture was stirred
  3. temperatureunder reflux for 16 h
  4. customThe cooled solution was evaporated
  5. customto remove solvent
  6. dissolutionThe mixture was dissolved in dichloromethane
  7. washwashed with a saturated aqueous solution of sodium chloride
  8. dry with materialdried over sodium sulfate
  9. customevaporated to dryness
  10. washrinsing with dichloromethane
  11. customAfter evaporation
  12. customthe resulting solid was triturated with diethyl ether

Sources & evidence

ORD record
ord-8dd1ac3cfc3d43479375cd626d195b58
Source dataset
uspto-grants-2012_06
Patent number
US08198287B2

Reaction notes

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